tbuckley/cabot-search huggingface dataset:
Are blood cytokines reliable biomarkers of allergic disease diagnosis and treatment responses?
Authors: Susanne Radonjic-Hoesli, Nikolay Pavlov, Hans-Uwe Simon, Dagmar Simon
Journal: Journal of Allergy and Clinical Immunology (2022)

With the development of targeted therapies for allergic diseases, the need for biomarkers supporting disease diagnosis and management has increased. Recent research has elucidated the pattern of cytokines and their distinct roles in the pathogenesis of allergic diseases. This means that cytokines should be considered as biomarkers. In this review article, we summarize published findings and critically discuss the use of cytokine measurements in association with disease diagnosis and management. Among the variety of suggested cytokines, thymus and activation-regulated chemokine (TARC) stands out and can indeed serve as a biomarker of atopic dermatitis. Both biologic characteristics and technical issues determine the reliability and limit the use of blood cytokines as biomarkers.
Table of Contents
Authors: Veronica Falconieri, William Busse, Ravi Viswanathan, Susanne Radonjic-Hoesli, Nikolay Pavlov, Hans-Uwe Simon, Dagmar Simon, Sunita Sharma, Ivana Yang, David Schwartz, Aurora Colo, Archana Shankar, Jaclyn Mcalees, Ian Lewkowich
Journal: Journal of Allergy and Clinical Immunology (2022)
Challenges of data sharing in European Covid-19 projects: A learning opportunity for advancing pandemic preparedness and response
Authors: Evelina Tacconelli, Anna Gorska, Elena Carrara, Ruth Joanna Davis, Marc Bonten, Alex W. Friedrich, Corinna Glasner, Herman Goossens, Jan Hasenauer, Josep Maria Haro Abad, José L. Peñalvo, Albert Sanchez-Niubo, Anastassja Sialm, Gabriella Scipione, Gloria Soriano, Yazdan Yazdanpanah, Ellen Vorstenbosch, Thomas Jaenisch
Journal: The Lancet Regional Health - Europe (2022)
Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder
Authors: Veera M. Rajagopal, Jinjie Duan, Laura Vilar-Ribó, Jakob Grove, Tetyana Zayats, J. Antoni Ramos-Quiroga, F. Kyle Satterstrom, María Soler Artigas, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Thomas D. Als, Anders Rosengren, Mark J. Daly, Benjamin M. Neale, Merete Nordentoft, Thomas Werge, Ole Mors, David M. Hougaard, Preben B. Mortensen, Marta Ribasés, Anders D. Børglum, Ditte Demontis
Journal: Nature Genetics (2022)
Molecular map of chronic lymphocytic leukemia and its impact on outcome
Authors: Binyamin A. Knisbacher, Ziao Lin, Cynthia K. Hahn, Ferran Nadeu, Martí Duran-Ferrer, Kristen E. Stevenson, Eugen Tausch, Julio Delgado, Alex Barbera-Mourelle, Amaro Taylor-Weiner, Pablo Bousquets-Muñoz, Ander Diaz-Navarro, Andrew Dunford, Shankara Anand, Helene Kretzmer, Jesus Gutierrez-Abril, Sara López-Tamargo, Stacey M. Fernandes, Clare Sun, Mariela Sivina, Laura Z. Rassenti, Christof Schneider, Shuqiang Li, Laxmi Parida, Alexander Meissner, François Aguet, Jan A. Burger, Adrian Wiestner, Thomas J. Kipps, Jennifer R. Brown, Michael Hallek, Chip Stewart, Donna S. Neuberg, José I. Martín-Subero, Xose S. Puente, Stephan Stilgenbauer, Catherine J. Wu, Elias Campo, Gad Getz
Journal: Nature Genetics (2022)
Breast cancer cell–derived microRNA-155 suppresses tumor progression via enhancing immune cell recruitment and antitumor function
Authors: Junfeng Wang, Quanyi Wang, Yinan Guan, Yulu Sun, Xiaozhi Wang, Kaylie Lively, Yuzhen Wang, Ming Luo, Julian A. Kim, E. Angela Murphy, Yongzhong Yao, Guoshuai Cai, Daping Fan
Journal: Journal of Clinical Investigation (2022)

Evidence suggests that increased microRNA-155 (miR-155) expression in immune cells enhances antitumor immune responses. However, given the reported association of miR-155 with tumorigenesis in various cancers, a debate is provoked on whether miR-155 is oncogenic or tumor suppressive. We aimed to interrogate the impact of tumor miR-155 expression, particularly that of cancer cell-derived miR-155, on antitumor immunity in breast cancer. We performed bioinformatic analysis of human breast cancer databases, murine experiments, and human specimen examination. We revealed that higher tumor miR-155 levels correlate with a favorable antitumor immune profile and better patient outcomes. Murine experiments demonstrated that miR-155 overexpression in breast cancer cells enhanced T cell influx, delayed tumor growth, and sensitized the tumors to immune checkpoint blockade (ICB) therapy. Mechanistically, miR-155 overexpression in breast cancer cells upregulated their CXCL9/10/11 production, which was mediated by SOCS1 inhibition and increased phosphorylated STAT1 (p-STAT1)/p-STAT3 ratios. We further found that serum miR-155 levels in breast cancer patients correlated with tumor miR-155 levels and tumor immune status. Our findings suggest that high serum and tumor miR-155 levels may be a favorable prognostic marker for breast cancer patients and that therapeutic elevation of miR-155 in breast tumors may improve the efficacy of ICB therapy via remodeling the antitumor immune landscape.
Rare genetic variants explain missing heritability in smoking
Authors: Seon-Kyeong Jang, Luke Evans, Allison Fialkowski, Donna K. Arnett, Allison E. Ashley-Koch, Kathleen C. Barnes, Diane M. Becker, Joshua C. Bis, John Blangero, Eugene R. Bleecker, Meher Preethi Boorgula, Donald W. Bowden, Jennifer A. Brody, Brian E. Cade, Brenda W. Campbell Jenkins, April P. Carson, Sameer Chavan, L. Adrienne Cupples, Brian Custer, Scott M. Damrauer, Sean P. David, Mariza de Andrade, Carla L. Dinardo, Tasha E. Fingerlin, Myriam Fornage, Barry I. Freedman, Melanie E. Garrett, Sina A. Gharib, David C. Glahn, Jeffrey Haessler, Susan R. Heckbert, John E. Hokanson, Lifang Hou, Shih-Jen Hwang, Matthew C. Hyman, Renae Judy, Anne E. Justice, Robert C. Kaplan, Sharon L. R. Kardia, Shannon Kelly, Wonji Kim, Charles Kooperberg, Daniel Levy, Donald M. Lloyd-Jones, Ruth J. F. Loos, Ani W. Manichaikul, Mark T. Gladwin, Lisa Warsinger Martin, Mehdi Nouraie, Olle Melander, Deborah A. Meyers, Courtney G. Montgomery, Kari E. North, Elizabeth C. Oelsner, Nicholette D. Palmer, Marinelle Payton, Anna L. Peljto, Patricia A. Peyser, Michael Preuss, Bruce M. Psaty, Dandi Qiao, Daniel J. Rader, Nicholas Rafaels, Susan Redline, Robert M. Reed, Alexander P. Reiner, Stephen S. Rich, Jerome I. Rotter, David A. Schwartz, Aladdin H. Shadyab, Edwin K. Silverman, Nicholas L. Smith, J. Gustav Smith, Albert V. Smith, Jennifer A. Smith, Weihong Tang, Kent D. Taylor, Marilyn J. Telen, Ramachandran S. Vasan, Victor R. Gordeuk, Zhe Wang, Kerri L. Wiggins, Lisa R. Yanek, Ivana V. Yang, Kendra A. Young, Kristin L. Young, Yingze Zhang, Dajiang J. Liu, Matthew C. Keller, Scott Vrieze
Journal: Nature Human Behaviour (2022)
Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism
Authors: C.M.M. de Jong, M. Blondon, C. Ay, A. Buchmuller, J. Beyer-Westendorf, J. Biechele, L. Bertoletti, G. Colombo, M.P. Donadini, S.V. Hendriks, L. Jara-Palomares, S. Nopp, P. Ruiz-Artacho, P. Stephan, C. Tromeur, T. Vanassche, P.E. Westerweel, F.A. Klok
Journal: Blood (2022)
The Heart in Modern Practice: Diagnosis and Treatment.
Journal: JAMA (1923)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19
Authors: Tobias Sinnberg, Christa Lichtensteiger, Omar Hasan Ali, Oltin T. Pop, Ann-Kristin Jochum, Lorenz Risch, Silvio D. Brugger, Ana Velic, David Bomze, Philipp Kohler, Pietro Vernazza, Werner C. Albrich, Christian R. Kahlert, Marie-Therese Abdou, Nina Wyss, Kathrin Hofmeister, Heike Niessner, Carl Zinner, Mara Gilardi, Alexandar Tzankov, Martin Röcken, Alex Dulovic, Srikanth Mairpady Shambat, Natalia Ruetalo, Philipp K. Buehler, Thomas C. Scheier, Wolfram Jochum, Lukas Kern, Samuel Henz, Tino Schneider, Gabriela M. Kuster, Maurin Lampart, Martin Siegemund, Roland Bingisser, Michael Schindler, Nicole Schneiderhan-Marra, Hubert Kalbacher, Kathy D. McCoy, Werner Spengler, Martin H. Brutsche, Boris Maček, Raphael Twerenbold, Josef M. Penninger, Matthias S. Matter, Lukas Flatz
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives: To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods: We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. Measurements and Main Results: IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19 but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. Conclusions: Our data suggest that patients with severe COVID-19 harbor IgA autoantibodies against pulmonary surfactant proteins B and C and that these autoantibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation.
Chemotherapy and Targeted Therapy for Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Rapid Recommendation Update
Authors: Beverly Moy, R. Bryan Rumble, Lisa A. Carey
Journal: Journal of Clinical Oncology (2022)

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.
Targeting the extra domain A of fibronectin for cancer therapy with CAR-T cells
Authors: Celia Martín-Otal, Aritz Lasarte-Cia, Diego Serrano, Noelia Casares, Enrique Conde, Flor Navarro, Inés Sánchez-Moreno, Marta Gorraiz, Patricia Sarrión, Alfonso Calvo, Carlos E De Andrea, José Echeveste, Amaia Vilas, Juan Roberto Rodriguez-Madoz, Jesús San Miguel, Felipe Prosper, Sandra Hervas-Stubbs, Juan Jose Lasarte, Teresa Lozano
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background One of the main difficulties of adoptive cell therapies with chimeric antigen receptor (CAR)-T cells in solid tumors is the identification of specific target antigens. The tumor microenvironment can present suitable antigens for CAR design, even though they are not expressed by the tumor cells. We have generated a CAR specific for the splice variant extra domain A (EDA) of fibronectin, which is highly expressed in the tumor stroma of many types of tumors but not in healthy tissues. Methods EDA expression was explored in RNA-seq data from different human tumor types and by immunohistochemistry in paraffin-embedded tumor biopsies. Murine and human anti-EDA CAR-T cells were prepared using recombinant retro/lentiviruses, respectively. The functionality of EDA CAR-T cells was measured in vitro in response to antigen stimulation. The antitumor activity of EDA CAR-T cells was measured in vivo in C57BL/6 mice challenged with PM299L-EDA hepatocarcinoma cell line, in 129Sv mice-bearing F9 teratocarcinoma and in NSG mice injected with the human hepatocarcinoma cell line PLC. Results EDA CAR-T cells recognized and killed EDA-expressing tumor cell lines in vitro and rejected EDA-expressing tumors in immunocompetent mice. Notably, EDA CAR-T cells showed an antitumor effect in mice injected with EDA-negative tumor cells lines when the tumor stroma or the basement membrane of tumor endothelial cells express EDA. Thus, EDA CAR-T administration delayed tumor growth in immunocompetent 129Sv mice challenged with teratocarcinoma cell line F9. EDA CAR-T treatment exerted an antiangiogenic effect and significantly reduced gene signatures associated with epithelial-mesenchymal transition, collagen synthesis, extracellular matrix organization as well as IL-6-STAT5 and KRAS pathways. Importantly, the human version of EDA CAR, that includes the human 41BB and CD3ζ endodomains, exerted strong antitumor activity in NSG mice challenged with the human hepatocarcinoma cell line PLC, which expresses EDA in the tumor stroma and the endothelial vasculature. EDA CAR-T cells exhibited a tropism for EDA-expressing tumor tissue and no toxicity was observed in tumor bearing or in healthy mice. Conclusions These results suggest that targeting the tumor-specific fibronectin splice variant EDA with CAR-T cells is feasible and offers a therapeutic option that is applicable to different types of cancer.
Covid-19: is omicron less lethal than delta?
Authors: Ramon Lorenzo-Redondo, Egon A Ozer, Judd F Hultquist
Journal: BMJ (2022)

Aim: To investigate the marital status and fertility in long-term survivors of high-grade osteosarcoma. Patients and Methods: We surveyed the marital rate (number of married persons/total number of persons) in 46 long-term survivors of osteosarcoma who were treated in our hospital between 1976 and 2002. In addition, we examined the fertility rate (number of persons having offspring/number of married persons) in 29 married patients. The participants were divided into 2 groups: one group (MC) in which moderate-dose chemotherapy was performed between 1976 and 1986; and another group (IC) in which intensive-dose chemotherapy was performed between 1987 and 2002. In each group, the fertility rate was investigated. As controls, we surveyed the marital and fertility rates in 52 siblings of the patients. Results: In the patients, the marital rate was 63.0% (29/46). There was no significant difference in the marital rate between the patients and their siblings. In the patients, the overall fertility rate was 58.6% (17/29). The fertility rate of male patients in the IC group (16.7%, 1/6) was significantly lower than that of their male siblings (76.5%, 13/17) (p=0.018). Conclusion: These results suggest that recently intensified chemotherapy for osteosarcoma affects fertility in long-term male survivors.
Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis
Authors: Marc B Stone, Zimri S Yaseen, Brian J Miller, Kyle Richardville, Shamir N Kalaria, Irving Kirsch
Journal: BMJ (2022)

Abstract Objectives To characterize individual participant level response distributions to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration from 1979 to 2016. Design Individual participant data analysis. Population 232 randomized, double blind, placebo controlled trials of drug monotherapy for major depressive disorder submitted by drug developers to the FDA between 1979 and 2016, comprising 73 388 adult and child participants meeting the inclusion criteria for efficacy studies on antidepressants. Main outcome measures Responses were converted to Hamilton Rating Scale for Depression (HAMD17) equivalent scores where other measures were used to assess efficacy. Multivariable analyses examined the effects of age, sex, baseline severity, and year of the study on improvements in depressive symptoms in the antidepressant and placebo groups. Response distributions were analyzed with finite mixture models. Results The random effects mean difference between drug and placebo favored drug (1.75 points, 95% confidence interval 1.63 to 1.86). Differences between drug and placebo increased significantly (P&lt;0.001) with greater baseline severity. After controlling for participant characteristics at baseline, no trends in treatment effect or placebo response over time were found. The best fitting model of response distributions was three normal distributions, with mean improvements from baseline to end of treatment of 16.0, 8.9, and 1.7 points. These distributions were designated Large, Non-specific, and Minimal responses, respectively. Participants who were treated with a drug were more likely to have a Large response (24.5% v 9.6%) and less likely to have a Minimal response (12.2.% v 21.5%). Conclusions The trimodal response distributions suggests that about 15% of participants have a substantial antidepressant effect beyond a placebo effect in clinical trials, highlighting the need for predictors of meaningful responses specific to drug treatment.
Meet the First Authors
Authors: Kanika Jain
Journal: Circulation Research (2022)

Her fascination with proteostasis and multifaceted Unfolded Protein Response (UPR) began during her PhD.As a postdoctoral fellow under the mentorship of Dr John Hwa, she became interested in the anucleate platelets.She now investigates the role of UPR and stress induced signaling in regulation of platelet function in cardiovascular diseases and beyond.
In This Issue
Authors: Ruth Williams
Journal: Circulation Research (2022)

Jain et al investigate the unfolded protein response in platelets.When a cell is stressed, it often accumulates clumps of misfolded proteins, which in turn trigger reduced protein translation and reprogramming of gene transcription-collectively known as the unfolded protein response (UPR).Because platelets have no nuclei, and thus no transcription, it was possible they lacked a UPR, but Jain and colleagues now show this is not the case.They found that treating human and mouse platelets with various stressors caused aggregations of misfolded proteins and induction of particular UPR factors.Oxidative stress, for example, induced the UPR kinase PERK, while an endoplasmic reticulum stressor induced a branch of the UPR involving transcription factor XBP1.The team went on to study the UPR in platelets from people with type II diabetes (DM)-in which platelet mediated thrombosis is a major complication.They showed that protein aggregation and upregulation of the XBP1 pathway in DM platelets correlated with disease severity.Furthermore, treating the DM platelets with a chemical chaperone-to aid correct protein folding-reduced protein aggregations and prevented the cells' pro-thrombotic activation.The work thus confirms that, even without transcription, platelets display stress-induced UPR and that targeting this response may be a way to reduce thrombosis risk in DM.
Evolution of Clinical Complexity, Treatment Burden, Health Care Use, and Diabetes-Related Outcomes Among Commercial and Medicare Advantage Plan Beneficiaries With Diabetes in the U.S., 2006–2018
Authors: Tyler J. Benning, Herbert C. Heien, Rozalina G. McCoy
Journal: Diabetes Care (2022)

OBJECTIVE To characterize trends in clinical complexity, treatment burden, health care use, and diabetes-related outcomes among adults with diabetes. RESEARCH DESIGN AND METHODS We used a nationwide claims database to identify enrollees in commercial and Medicare Advantage plans who met claims criteria for diabetes between 1 January 2006 and 31 March 2019 and to quantify annual trends in clinical complexity (e.g., active health conditions), treatment burden (e.g., medications), health care use (e.g., ambulatory, emergency department [ED], and hospital visits), and diabetes-related outcomes (e.g., hemoglobin A1c [HbA1c] levels) between 2006 and 2018. RESULTS Among 1,470,799 commercially insured patients, the proportion with ≥10 active health conditions increased from 33.3% (95% CI 33.1–33.4) in 2006 to 38.9% (38.8–39.1) in 2018 (P = 0.001) and the proportion taking three or more glucose-lowering medications increased from 11.6% (11.5–11.7) to 23.1% (22.9–23.2) (P = 0.007). The proportion with HbA1c ≥8.0% (≥64 mmol/mol) increased from 28.0% (27.7–28.3) in 2006 to 30.5% (30.2–30.7) in 2015, decreasing to 27.8% (27.5–28.0) in 2018 (overall trend P = 0.04). Number of ambulatory visits per patient per year decreased from 6.86 (6.84–6.88) to 6.19 (6.17–6.21), (P = 0.001) while ED visits increased from 0.26 (0.257–0.263) to 0.29 (0.287–0.293) (P = 0.001). Among 1,311,903 Medicare Advantage enrollees, the proportion with ≥10 active conditions increased from 51.6% (51.2–52.0) to 65.1% (65.0–65.2) (P &amp;lt; 0.001); the proportion taking three or more glucose-lowering medications was stable at 16.6% (16.3–16.9) and 18.1% (18.0–18.2) (P = 0.98), and the proportion with HbA1c ≥8.0% increased from 17.4% (16.7–18.1) to 18.6% (18.4–18.7) (P = 0.008). Ambulatory visits per patient per year remained stable at 8.01 (7.96–8.06) and 8.17 (8.16–8.19) (P = 0.23), but ED visits increased from 0.41 (0.40–0.42) to 0.66 (0.66–0.66) (P &amp;lt; 0.001). CONCLUSIONS Among patients with diabetes, clinical complexity and treatment burden have increased over time. ED utilization has also increased, and patients may be using ED services for low-acuity conditions.